Medical Management of Late Intrauterine Death.

NCT02488642 | Completed Phase 4

• 1 other identifier: 212250-29021
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the therapeutic efficacy and safety of isosorbide dinitrate-oxytocin in combination in the management of late intrauterine foetal death.

Conditions

Cervical Pregnancy; Maternal Care for Late Fetal Death

Keywords

Isosorbide dinitrate gel solution; late intrauterine death; nitric oxide donors

Outcome Measures

Primary Outcomes (1)

• Rates of uterine expulsion in the women who received the isosorbide dinitrate-oxytocin regimen

  within 15 hours of administration

Secondary Outcomes (1)

• A Bishop score of >7 of administration of the first dose of isosorbide dinitrate

  within 12 hours

Study Arms (2)

isosorbide dinitrate-oxytocin

EXPERIMENTAL

Preinduction with isosorbide dinitrate gel solution (80 mg/1.5 mL) were administered in the posterior fornix every 3 hours. Once a Bishop score of over 7 was reached, oxytocin was infused in a balanced electrolyte solution beginning with an infusion rate of 2 milli-International Units per minute (mIU/min) and doubling the dose every 15 minutes. If the cervical conditions (\<7 Bishop Score) did not change after the treatment application, a new dose, without exceeding 4 doses, to facilitate cervical ripening.

Drug: Isosorbide Dinitrate; Drug: Oxytocin

misoprostol-oxytocin

PLACEBO COMPARATOR

Preinduction with misoprostol gel solution (100 mcg/1.5 mL) were administered in the posterior fornix every 3 hours. Once a Bishop score of over 7 was reached, oxytocin was infused in a balanced electrolyte solution beginning with an infusion rate of 2 milli-International Units per minute (mIU/min) and doubling the dose every 15 minutes. If the cervical conditions (\<7 Bishop score) did not change after the treatment application, participants received a new dose, without exceeding 4 doses, to facilitate cervical ripening.

Drug: Misoprostol; Drug: Oxytocin

Interventions

Isosorbide Dinitrate DRUG

Also known as: Isordil, Dilatrate-SR, Sorbitrate

isosorbide dinitrate-oxytocin

Misoprostol DRUG

Also known as: Cytotec

misoprostol-oxytocin

Oxytocin DRUG

Oxytocin was infused in a balanced electrolyte solution beginning with an infusion rate of 2 milli-International Units per minute (mIU/min) and doubling the dose every 15 minutes.

isosorbide dinitrate-oxytocin; misoprostol-oxytocin

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Closed cervix without evidence of cervical dilation or baseline uterine activity.
• A Bishop score of \<5, having intact membranes.
• Gestation greater than or equal to 20 weeks established by the date of menstruation or by fetometry and ultrasound-confirmed late IUFD.

You may not qualify if:

• Multiple pregnancies.
• IUFD after late foeticide or the management of specific medical conditions associated with an increase in the risk of IUFD.
• Patients with a history of hypertension.
• Women with a history of unexplained antepartum haemorrhage, pelvic dystocia or any another counter-indications where medications were used.

Sponsors & Collaborators

• National Institute of Perinatology: lead
• National Council of Science and Technology, Mexico: collaborator

Related Publications (30)

• World Health Organization. Induction and augmentation of labour. In: WHO, UNFPA, UNICEF, World Bank, editor. Managing Complications in Pregnancy and Childbirth: A Guide for Midwives and Doctors. Geneva: WHO; 2000. pp. 17-25.

  BACKGROUND

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  PMID: 11336776 RESULT

• Neiger R, Greaves PC. Comparison between vaginal misoprostol and cervical dinoprostone for cervical ripening and labor induction. Tenn Med. 2001 Jan;94(1):25-7.

  PMID: 11194687 RESULT

• Bolnick JM, Velazquez MD, Gonzalez JL, Rappaport VJ, McIlwain-Dunivan G, Rayburn WF. Randomized trial between two active labor management protocols in the presence of an unfavorable cervix. Am J Obstet Gynecol. 2004 Jan;190(1):124-8. doi: 10.1016/s0002-9378(03)00952-9.

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• Khan RU, El-Refaey H, Sharma S, Sooranna D, Stafford M. Oral, rectal, and vaginal pharmacokinetics of misoprostol. Obstet Gynecol. 2004 May;103(5 Pt 1):866-70. doi: 10.1097/01.AOG.0000124783.38974.53.

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• Ignarro LJ, Lippton H, Edwards JC, Baricos WH, Hyman AL, Kadowitz PJ, Gruetter CA. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther. 1981 Sep;218(3):739-49. No abstract available.

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• Schmidt HH, Lohmann SM, Walter U. The nitric oxide and cGMP signal transduction system: regulation and mechanism of action. Biochim Biophys Acta. 1993 Aug 18;1178(2):153-75. doi: 10.1016/0167-4889(93)90006-b. No abstract available.

  PMID: 7688574 RESULT

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• Chung SJ, Fung HL. Identification of the subcellular site for nitroglycerin metabolism to nitric oxide in bovine coronary smooth muscle cells. J Pharmacol Exp Ther. 1990 May;253(2):614-9.

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• Michel T, Smith TW. Nitric oxide synthases and cardiovascular signaling. Am J Cardiol. 1993 Sep 9;72(8):33C-38C. doi: 10.1016/0002-9149(93)90253-9.

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• Wagaarachchi PT, Ashok PW, Narvekar NN, Smith NC, Templeton A. Medical management of late intrauterine death using a combination of mifepristone and misoprostol. BJOG. 2002 Apr;109(4):443-7. doi: 10.1111/j.1471-0528.2002.01238.x.

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• Espey MG, Miranda KM, Feelisch M, Fukuto J, Grisham MB, Vitek MP, Wink DA. Mechanisms of cell death governed by the balance between nitrosative and oxidative stress. Ann N Y Acad Sci. 2000;899:209-21. doi: 10.1111/j.1749-6632.2000.tb06188.x.

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• Lokugamage AU, Forsyth SF, Sullivan KR, El Refaey H, Rodeck CH. Randomized trial in multiparous patients: investigating a single vs. two-dose regimen of intravaginal misoprostol for induction of labor. Acta Obstet Gynecol Scand. 2003 Feb;82(2):138-42. doi: 10.1034/j.1600-0412.2003.00084.x.

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• Cabrol D, Dubois C, Cronje H, Gonnet JM, Guillot M, Maria B, Moodley J, Oury JF, Thoulon JM, Treisser A, et al. Induction of labor with mifepristone (RU 486) in intrauterine fetal death. Am J Obstet Gynecol. 1990 Aug;163(2):540-2. doi: 10.1016/0002-9378(90)91193-g.

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• Hofmeyr GJ, Gulmezoglu AM, Pileggi C. Vaginal misoprostol for cervical ripening and induction of labour. Cochrane Database Syst Rev. 2010 Oct 6;2010(10):CD000941. doi: 10.1002/14651858.CD000941.pub2.

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• Bartha JL, Comino-Delgado R, Garcia-Benasach F, Martinez-Del-Fresno P, Moreno-Corral LJ. Oral misoprostol and intracervical dinoprostone for cervical ripening and labor induction: a randomized comparison. Obstet Gynecol. 2000 Sep;96(3):465-9. doi: 10.1016/s0029-7844(00)00954-6.

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• Nicoll AE, Mackenzie F, Greer IA, Norman JE. Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: a randomized controlled trial to determine effects on maternal and fetal hemodynamics. Am J Obstet Gynecol. 2001 Apr;184(5):958-64. doi: 10.1067/mob.2001.111797.

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• Arteaga-Troncoso G, Chacon-Calderon AE, Martinez-Herrera FJ, Cruz-Nunez SG, Lopez-Hurtado M, Belmont-Gomez A, Guzman-Grenfell AM, Farfan-Labonne BE, Neri-Mendez CJ, Zea-Prado F, Guerra-Infante FM. A randomized controlled trial comparing isosorbide dinitrate-oxytocin versus misoprostol-oxytocin at management of foetal intrauterine death. PLoS One. 2019 Nov 21;14(11):e0215718. doi: 10.1371/journal.pone.0215718. eCollection 2019.

  PMID: 31751343 DERIVED

MeSH Terms

Interventions

Isosorbide Dinitrate; Isosorbide; Misoprostol; Oxytocin

Intervention Hierarchy (Ancestors)

Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Gabriel Arteaga-Troncoso, PhD.

  National Institute of Perinatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Researcher

Study Record Dates

• First Submitted: June 26, 2015
• First Posted: July 2, 2015
• Study Start: May 1, 2008
• Primary Completion: September 1, 2013
• Study Completion: May 1, 2014
• Last Updated: July 24, 2015

Record last verified: 2015-07